The interaction of calmodulin with the adenylate cyclase of Bordetella pertussis has been further investigated. The enzyme is activated by the regulator protein in two distinct modes: Ca++ dependent at high sensitivity and Ca++ independent at lower sensitivity. The calmoculin concentration required is decreased by 100-200-fold by the presence of calcium. There is, in addition, an inhibition by a tightly bound metal ion, not yet identified, that can be relieved by o-phenanthroline. These effects may be due to two adenylate cyclases since we have succeeded in isolating a Ca++ independent form. We have also started investigating the action of factors in B. pertussis that can modulate eukaryotic adenylate cyclases such as pertussis toxin and endotoxin.